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At least 19 recordsLinked to original sources
PubMed2005

Double-stranded RNA induces sequence-specific antiviral silencing in addition to nonspecific immunity in a marine shrimp: convergence of RNA interference and innate immunity in the invertebrate antiviral response?

Double-stranded RNA (dsRNA) is a common by-product of viral infections and a potent inducer of innate antiviral immune responses in vertebrates. In the marine shrimp Litopenaeus vannamei, innate antiviral immunity is also induced by dsRNA in a sequence-independent manner. In this study, the hypothesis that dsRNA can evoke not only innate antiviral immunity but also a sequence-specific antiviral response in shrimp was tested. It was found that viral sequence-specific dsRNA affords potent antiviral immunity in vivo, implying the involvement of RNA interference (RNAi)-like mechanisms in the antiviral response of the shrimp. Consistent with the activation of RNAi by virus-specific dsRNA, endogenous shrimp genes could be silenced in a systemic fashion by the administration of cognate long dsRNA. While innate antiviral immunity, sequence-dependent antiviral protection, and gene silencing could all be induced by injection of long dsRNA molecules, injection of short interfering RNAs failed to induce similar responses, suggesting a size requirement for extracellular dsRNA to engage antiviral mechanisms and gene silencing. We propose a model of antiviral immunity in shrimp by which viral dsRNA engages not only innate immune pathways but also an RNAi-like mechanism to induce potent antiviral responses in vivo.

Animals↗
PubMed1991

Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities.

Considerable progress has been made in the understanding of the molecular biology of the human interferon system. The genes encoding the interferons, their receptors, and the proteins that mediate many of their biological effects have been molecularly cloned and characterized. The availability of complete cDNA clones of components of the interferon systems has contributed significantly to our understanding of both the biology and the biochemistry of the antiviral actions of interferons. At the biological level, the antiviral effects of interferon may be viewed to be virus-type nonspecific. That is, treatment of cells with one type or even subspecies of interferon often leads to the generation of an antiviral state effective against a wide array of different RNA and DNA animal viruses. However, at the biochemical level, the antiviral action of interferon is often virus-type selective. That is, the apparent molecular mechanism which is primarily responsible for the inhibition of virus replication may differ considerably between virus types, and even host cells. For example, the IFN-regulated Mx protein selectively inhibits influenza virus but not other viruses when constitutively expressed in mouse cells. The IFN-regulated 2',5'-oligoadenylate synthetase selectively inhibits EMC and mengo viruses, two picornaviruses, but not viruses of other families when constitutively expressed in transfected cells. Some viruses are typically insensitive to the antiviral effects of interferon, both in cell culture and in intact animals. This lack of sensitivity to IFN may result from a virus-mediated direct antagonism of the interferon system. For example, in the case of adenovirus, the activation of the IFN-regulated RNA-dependent P1/elF-2 protein kinase is blocked by the virus-associated VA RNA. The relative sensitivity to interferon of different animal viruses varies appreciably. All three of the basic components required to measure an antiviral response may play a role in determining the relative effectiveness of the antiviral response: the species of interferon administered; the kind of cell treated; and, the type of virus used to challenge the interferon-treated host cell. Thus, the relative sensitivity to interferon observed for a particular interferon-cell-virus combination is likely the result of the equilibrium between the many agonists and antagonists which contribute to the overall response. That is, the relative sensitivity of a virus to the inhibitory action of IFN is governed by the qualitative nature and quantitative amount of the individual IFN-regulated cell proteins that may collectively contribute to the inhibition of virus replication.(ABSTRACT TRUNCATED AT 400 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1995

Antiviral activity of a phosphorothioate oligonucleotide complementary to human cytomegalovirus RNA when used in combination with antiviral nucleoside analogs.

ISIS 2922 is a phosphorothioate oligonucleotide with potent antiviral activity against human cytomegalovirus (HCMV) in cell culture assays. The ability of ISIS 2922 to inhibit replication of HCMV when used in combination with other antiviral agents approved for treatment of HCMV disease was investigated using a 96-well immunoassay. The antiviral activity of ISIS 2922 against HCMV was additive with that of ganciclovir (9-(1,3-dihydroxy-2-propoxymethylguanine); DHPG) or foscarnet (phosphonoformate). Compounds used clinically for the treatment of human immunodeficiency virus infection and likely to be co-administered with ISIS 2922 in the clinic were also evaluated for their ability to modulate the antiviral activity of ISIS 2922. 3'-Azido-3'-deoxythymidine (AZT) exhibited no antiviral activity against HCMV in the 96-well immunoassay, and did not significantly alter the antiviral activity of ISIS 2922. 2'-3'-Dideoxycytidine (ddC) was able to inhibit replication of HCMV at high doses, and this activity was additive with that of ISIS 2922. ISIS 2922 inhibited HIV replication in acute infection assays at relatively high concentrations as previously reported for non-complementary phosphorothioate oligonucleotides. When ISIS 2922 was used in combination with AZT in this assay, interactions were additive at most concentrations, although significant and reproducible synergy was observed at some concentration combinations.

Antiviral Agents↗
PubMed1985

Studies on antiviral agents. II. Synthesis and in vitro antiviral activity on new kanamycin A derivatives having higher acyl group at N-1 position.

The synthesis and antiviral activity of 3''-N-trifluoroacetylkanamycin A derivatives (6) having higher acyl group at the N-1 position are described. On the basis of the structure-activity relationships between antiviral activity and alkyl chain length in an acyl group at the N-1 position, analogs (6f approximately I) having higher alkylcarbonyl group exhibited antiviral activity against not only HSV-I but also influenza virus. Analogs (6q approximately v) having higher alkyloxycarbonyl group showed antiviral activity against HSV-I. In addition, kanamycin A derivatives (6n, o, y, z) possessing higher alkylcarbonyl group with a functional group, higher alkylaminocarbonyl group, and higher alkylthiocarbonyl group had antiviral activity against HSV-I. The analog (6h) showed a broad antiviral spectrum against both DNA (HSV-I, HSV-II, VZV) and RNA (influenza) viruses.

Antiviral Agents↗
PubMed1996

Transfer of antivirals to skin Langerhans cells--a novel approach to anti-HIV treatment by "antiviral peplotion".

The analysis of the history of the research on antivirals especially the treatment of HIV-1 infected individuals with antivirals which were developed prior to the current AIDS epidemic led to suggest a different approach to the targeting of antivirals in the AIDS patients. Since HIV-1 replication in infected individuals occurs in the lymph nodes, it is suggested that modified anti-HIV-1 drugs should be applied to Langerhans cells in the skin. The Langerhans cells can serve as the carries of the antiviral drugs attached to their surfaces due to their ability to migrate from the skin through the lymph vessels and to home to the lymph node. At that site Langerhans cells interact with T cells. Transfer of the anti-HIV-1 drugs to infected CD4+ T cells in the lymph node will reduce virus replication in the lymph nodes and will reduce the cytotoxic systemic effects of the antiviral drug. Such an antiviral treatment requires the development of efficient methods of drug delivery through the skin.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy.

Following the discovery of the first effective antiviral compound (idoxuridine) in 1959, nucleoside analogues, especially acyclovir (ACV) for the treatment of herpesvirus infections, have dominated antiviral therapy for several decades. However, ACV and similar acyclic nucleosides suffer from low aqueous solubility and low bioavailability following oral administration. Derivatives of acyclic nucleosides, typically esters, were developed to overcome this problem and valaciclovir, the valine ester of ACV, was among the first of a new series of compounds that were readily metabolized upon oral administration to produce the antiviral nucleoside in vivo, thus increasing the bioavailility by several fold. Concurrently, famciclovir was developed as an oral formulation of penciclovir. These antiviral 'prodrugs' thus established a principle that has led to many successful drugs including both nucleoside and nucleotide analogues for the control of several virus infections, notably those caused by herpes-, retro- and hepatitisviruses. This review will chart the origins and development of the most important of the antiviral prodrugs to date.

Animals↗
PubMed2006

Antiviral Chemistry & Chemotherapy's current antiviral agents FactFile 2006 (1st edition).

The number of useful antiviral compounds is rapidly expanding. The current antiviral agents FactFile is a convenient key to the vital statistics of antiviral compounds to be used as an aide mémoire when reading or writing antiviral literature. A mini-portrait is provided for each of the antiviral compounds. The minimum criteria for inclusion of new compounds in the FactFile is the granting of an investigational new drug application with the realistic potential for medical or veterinary application. Several compounds that were subsequently withdrawn from further development are also included because of their historical importance or particular interest. The compounds are listed alphabetically according to their generic names together with systematic chemical names, common names and chemical structures. The compounds are grouped by virus targets; thus, the list is sub-divided into inhibitors of DNA viruses, RNA viruses, and retroviruses. The authors welcome comments and suggestions to be incorporated in future editions of the FactFile.

Antiviral Agents↗
PubMed1985

Studies on antiviral agents. III. Synthesis and in vitro antiviral activity of 1-N-higher-acyl-3"-N-functionalized acylkanamycin A derivatives.

The synthesis and antiviral activity of 1-N-palmitoyl- or 1-N-(3-hydroxytetradecanoyl)-kanamycin A derivatives (7,8) having various type of acyl substituents at the N-3" position were investigated. The structure-activity relationships between the antiviral activity and the substituent at the N-3" position is described. In this series, 3"-N-acetyl-1-N-palmitoyl-kanamycin A (7c) showed the excellent antiviral activity against HSV-I and influenza virus. Further, we examined the synthesis and the antiviral activity of 3"-N-glycylkanamycin A derivatives (9) having a higher-acyl group at the N-1 position. The 3"-N-glycyl-1-N-pentadecanoylkanamycin A (9a) also exhibited excellent antiviral activity.

Amikacin↗
PubMed1994

Pokeweed antiviral protein inactivates pokeweed ribosomes; implications for the antiviral mechanism.

Pokeweed antiviral protein (PAP) and other ribosome-inactivating proteins (RIPs) had previously been thought to be incapable of attacking conspecific ribosomes, thus having no effect on endogenous processes. This assertion conflicts with a model for PAP's in vivo antiviral mechanism in which PAP (a cell wall protein) selectively enters virus-infected cells and disrupts protein synthesis, thus causing local suicide and preventing virus replication. We show here that pokeweed (Phytolacca americana) ribosomes, as well as endod (Phytolacca dodecandra) ribosomes, are indeed highly sensitive to inactivation by conspecific RIPs. Ribosomes isolated from RIP-free pokeweed and endod suspension culture cells were found to be highly active in vitro, as measured by poly(U)-directed polyphenylalanine synthesis. Phytolacca ribosomes challenged with conspecific RIPs generated dose-response curves (IC50 of 1 nM PAP or dodecandrin) very similar to those from wheat germ ribosomes. To determine if Phytolacca cells produce a cytosolic 'anti-RIP' protective element, ribosomes were combined with Phytolacca postribosomal supernatant factors from culture cells, then challenged with conspecific RIPs. Resulting IC50 values of 3-7 nM PAP, PAP-II, PAP-S or dodecandrin indicate that supernatants from these Phytolacca cells lack a ribosomal protective element. This research demonstrates that PAP inactivates pokeweed ribosomes (and is therefore potentially toxic to pokeweed cells) and supports the local suicide model for PAP's in vivo antiviral mechanism. The importance of spatial separation between PAP and ribosomes of cells producing this RIP is emphasized, particularly if crop plants are transformed with the PAP gene to confer antiviral protection.

Antiviral Agents↗
PubMed2002

In vitro antiviral activity of aphidicolin and its derivates. Synergistic effects of aphidicolin with other antiviral drugs.

Twenty derivatives of aphidicolin were tested against HSV (herpes simplex virus), HCMV (human cytomegalovirus) and adenovirus in vitro. In addition, the antiviral activity of aphidicolin (CAS 38966-21-1) in combination with aciclovir (CAS 59277-89-3) or cidofovir (CAS 113852-37-2) against HSV was determined. The antiviral effects were evaluated using plaque reduction assay in Vero cells or human Foreskin Fibroblasts (HFF) for HSV and HCMV, respectively. Combination indexes were calculated using the method of Chou and Talalay. Two derivatives (K14254 and K14266) that are considered to be prodrugs of aphidicolin were shown to inhibit HCMV and HSV replication comparably to aphidicolin. None of the tested substances inhibited adenovirus replication. Aphidicolin acted synergistically with aciclovir in a 1:1 molar ratio and with cidofovir in different ratios. Aphidicolin and its two antiviral active derivatives might represent useful additional tools for antiviral therapy of HSV and HCMV infections, especially in combination with clinically used drugs.

Adenoviridae↗
PubMed2000

Antiviral substance from silkworm faeces: characterization of its antiviral activity.

The antiviral activity of a substance (L4-1) purified from silkworm faeces was examined in an HVJ (Sendai virus)-LLC-MK2 cell system. Its antiviral effect depended on the period of light irradiation and was inhibited by sodium sulfite and anaerobic conditions. These results indicate that the antiviral activity of L4-1 is associated with active oxygen species produced from the substance. SDS-polyacrylamide gel electrophoretic analysis showed that viral proteins were damaged by this substance under light irradiation. The results suggest that the antiviral activity is due to damage to viral protein(s) caused by active oxygen species produced from L4-1.

Animals↗
PubMed1983

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent.

The relative in vitro antiviral activities of three related nucleoside carboxamides, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), and selenazole (2-beta-D-ribofuranosylselenazole-4-carboxamide), were studied against selected DNA and RNA viruses. Although the activity of selenazole against different viruses varied, it was significantly more potent than ribavirin and tiazofurin against all tested representatives of the families Paramyxoviridae (parainfluenza virus type 3, mumps virus, measles virus), Reoviridae (reovirus type 3), Poxviridae (vaccinia virus), Herpes-viridae (herpes simplex virus types 1 and 2), Togaviridae (Venezuelan equine encephalomyelitis virus, yellow fever virus, Japanese encephalitis virus), Bunyaviridae (Rift Valley fever virus, sandfly fever virus [strain Sicilian], Korean hemorrhagic fever virus), Arenaviridae (Pichinde virus), Picornaviridae (coxsackieviruses B1 and B4, echovirus type 6, encephalomyocarditis virus), Adenoviridae (adenovirus type 2), and Rhabdoviridae (vesicular stomatitis virus). The antiviral activity of selenazole was also cell line dependent, being greatest in HeLa, Vero-76, and Vero E6 cells. Selenazole was relatively nontoxic for Vero, Vero-76, Vero E6, and HeLa cells at concentrations of up to 1,000 micrograms/ml. The relative plating efficiency at that concentration was over 90%. The effects of selenazole on viral replication were greatest when this agent was present at the time of viral infection. The removal of selenazole from the medium of infected cells did not reverse the antiviral effect against vaccinia virus, but there was a gradual resumption of viral replication in cells infected with parainfluenza type 3 or herpes simplex virus type 1 (strain KOS). However, the antiviral activity of ribavirin against the same viruses was reversible when the drug was removed.

Animals↗
PubMed2000

Effects of antiviral usage on transmission dynamics of herpes simplex virus type 1 and on antiviral resistance: predictions of mathematical models.

Herpes simplex virus type 1 (HSV-1) causes recurrent herpes labialis (RHL), a common disease afflicting up to 40% of adults worldwide. Mathematical models are used to analyze the effect of antiviral treatment on the transmission of, and the prevalence of drug resistance in, HSV-1 in the United States. Three scenarios are analyzed: no antiviral use, the current level of use, and a substantial increase in nucleoside analogue use, such as might occur if topical penciclovir were available over-the-counter for the treatment of RHL. A basic model predicts that present level of nucleoside analogue use has a negligible effect on HSV-1 transmission and that even if use of topical penciclovir for (RHL) increased substantially, the overall prevalence of infectious HSV-1 is unlikely to be reduced by more than 5%. An expanded model, which allows for acquired resistance and includes immunocompromised hosts and other more realistic features, predicts that current antiviral use is unlikely to lead to any noticeable increase in resistance. If antiviral use increases, the resulting rise in resistance in the population will depend primarily on the probability that immunocompetent hosts will acquire permanent resistance upon treatment. This probability is known to be small, but its exact value remains uncertain. If acquired resistance occurs less than once per 2,500 treated episodes, then in the community at large, the frequency of HSV-1 resistance is predicted to increase slowly, if at all (remaining below 0.5% for >50 years), even with extensive nucleoside analogue use. If acquired resistance emerges in 1 of 625 treated episodes (the maximum of an approximate 95% confidence interval derived from the results of several studies of resistance in treated hosts), then the prevalence of infection with resistant HSV-1 could rise from about 0.2% to 1.5 to 3% within 50 years. The limitations of existing data on acquired resistance and the potential impact of acquired resistance if it occurs are discussed, and strategies are suggested for enhancing information on acquired resistance. The predictions of this model contrast with the more rapid increases in antimicrobial resistance anticipated by models and observed for other pathogenic bacteria and viruses. The reasons for these contrasting predictions are discussed.

Aging↗
PubMed1999

[Vasculitis associated with antiviral vaccines and antiviral agents].

There is firm evidence that several viruses can cause systemic vasculitis. Vasculitis induced by antiviral vaccines and drugs is less common and less well know. Most cases consist in de novo vasculitis that resolves spontaneously or under steroid therapy. Thus, the outcome is usually favorable. If an antiviral drug is the cause, it should not be used again in the patient. Another common sense measure is to refrain from immunizing patients with active vasculitis. A recent history of antiviral immunization or antiviral drug treatment should be sought routinely as part of the etiologic work-up of every patient with vasculitis.

Acyclovir↗
PubMed2002

[Antiviral and non-antiviral general treatments for oro-facial and genital herpes (pregnancy and neonates excluded)].

General treatments for immunocompetent individuals with herpes simplex infections are based on the use of antiviral agents which constitute the only treatment with proven efficacy. Antivirals were developed in the 1980s with aciclovir (ACV) as the leading compound and have greatly changed management. However, once the virus has penetrated the organism, it cannot be eradicated, neither by the immune system nor by antiviral agents. This viral resistance is basically related to its capacity to maintain itself in a latent form in the sensorial ganglions. ACV is the first line treatment, used since the 1980s; other antiviral agents are also available.

Acyclovir↗
PubMed1975

[Experimental results with systematically synthetized substances for antiviral chemotherapy / 4th communication: The role of physical binding in the synthesis of antiviral chemotherapeutics and its influence on potential mutagenic effects (author's transl)].

13 antiviral substances containing specific hydrogen bridge linkage systems out of the classes of 2-substituted 4-phenylthiazoles, 4-phenylimidazoles and indandiones-(1,3) were tested for their mutagenic potency in the host-mediated assay, in bone marrow of rats, in spermatogonia of mice and in the micronucleus test of rats. Only one substance, N1-methyl-N2-[4-phenylthiazolyl-(2)]-urea, was found to be mutagenic. This fact substantiates the hypothesis that the antiviral effectiveness of the substances is not caused by a chemical change in the coding system but by forming "physical" linkages like hydrogen bridge complexes with coding structures. Altogether 159 compounds of very different structures were investigated for their antiviral chemotherapeutic potency in 893 tests in cell cultures and 461 animal tests. It can be stated that compounds with a low molecular weight containing the "effective structures" (see article) show a larger yield of antiviral compounds than do substances without these structures (about 50% positive results in cell cultures and 25% in animals 15% and 0%, respectively).

Animals↗